Document Detail

Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase.
MedLine Citation:
PMID:  21469138     Owner:  NLM     Status:  MEDLINE    
km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.
Nageswara R Pulipati; Qunyan Jin; Xin Liu; Baodong Sun; Manoj K Pandey; Jonathan P Huber; Wei Ding; Kathleen M Mulder
Related Documents :
21352228 - Amyloid-beta oligomers increase the localization of prion protein at the cell surface.
25414138 - Distinct functions of epidermal and myeloid derived vegf-a in skin tumorigenesis mediat...
25322778 - Phenylenevinylene conjugated oligoelectrolytes as fluorescent dyes for mammalian cell i...
25412308 - Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced ol...
24894628 - Biofilms, flagella, and mechanosensing of surfaces by bacteria.
12008058 - Dimers from dechlorinated rebeccamycin: synthesis, interaction with dna, and antiprolif...
Publication Detail:
Type:  Journal Article     Date:  2011-04-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  129     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-05-27     Completed Date:  2011-07-27     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Division
Cell Line, Tumor
Cytoplasmic Dyneins / metabolism*
Dyneins / metabolism*
Mice, Nude
Neoplasm Transplantation
Ovarian Neoplasms / metabolism*,  prevention & control
Transplantation, Heterologous
Grant Support
R01 CA090765/CA/NCI NIH HHS; R01 CA090765-10/CA/NCI NIH HHS; R01 CA092889/CA/NCI NIH HHS; R01 CA092889-08S1/CA/NCI NIH HHS; R01 CA092889-10/CA/NCI NIH HHS; R01 CA100239/CA/NCI NIH HHS; R01 CA100239-05/CA/NCI NIH HHS
Reg. No./Substance:
0/DYNLRB1 protein, human; EC Dyneins; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Mitochondria: sovereign of inflammation?
Next Document:  Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical...